There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Ro 40-5967 is a new calcium channel antagonist that binds at the same membrane sites
as verapamil, yet has minimal negative inotropic effects. The effects of Ro 40-5967
on the susceptibility to ventricular fibrillation were investigated and compared to
diltiazem. Ventricular fibrillation (VF) was induced in 40 mongrel dogs with healed
myocardial infarctions by a 2-min coronary occlusion during exercise. Twenty-four
animals were found to be susceptible to VF and were given the treatments described
below. Pretreatment with Ro 40-5967 (n = 17, 1000 micrograms/kg i.v.) significantly
(P < 0.001) reduced the incidence of VF (13 of 17 protected) during the exercise plus
ischemia test. Diltiazem (n = 8, 1000 micrograms/kg) completely suppressed VF. Lower
doses of diltiazem and Ro 40-5967 did not prevent VF. The hemodynamic effects of Ro
40-5967 were also compared to diltiazem and verapamil. Diltiazem and verapamil, but
not Ro 40-5967, increased P-R interval in a dose-dependent manner. Even when reflex
tachycardia was controlled by beta-adrenoceptor blockade, Ro 40-5967 still exerted
only minimal effects on P-R interval. Verapamil, but neither Ro 40-5967 nor diltiazem,
provoked a dose-dependent negative inotropic response. All three drugs elicited large
increases in coronary blood flow. These data support the hypothesis that calcium entry
may play a critical role in the development of malignant arrhythmias during ischemia.
Further, Ro 40-5967 can protect against ventricular fibrillation without significant
negative inotropic or dromotropic effects.